Protection against 7,12-dimethylbenzanthracene-induced tumour initiation by protein A in mouse skin.

Protein A is an immunostimulating glycoprotein obtained from Staphylococcus aureus Cowan I. Its antitumour activity is proven in various tumour models. Its ability to provide protection against tumour initiation by the chemical carcinogen 7,12-dimethylbenzanthracene (DMBA) has been investigated in the present study using a mouse skin model of two-stage carcinogenesis. Protein A was administered intraperitoneally (1 microgram/animal 20 g body wt.) twice a week for 2 weeks, prior to initiation by DMBA. The promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) (3 or 5 micrograms/animal in 100 microliters acetone). Protein A provided significant protection to animals from DMBA-induced tumour initiation as was observed by the decrease in cumulative number of tumours, percent of animals developing tumours, number of tumours per animal and rate of tumour growth. Our data indicate that protein A has anticarcinogenic properties.     

End-to-side anastomosis of rat carotid artery: comparison of different types of section and shape of the terminal end

Summary In 50 rats, different types of end-to-side carotid artery anastomoses were compared. In one technique, a longitudinal split in the long axis of the vessel was performed to enhance the diameter of the anastomosis. This theoretical advantage was not confirmed in this series. The clamping time, anastomoses time, and tamponade time were increased significantly when compared with a simple, slightly oblique end-to-side anastomosis. This study highlighted that the most simple type of end-to-side anastomosis gave less bleeding, achieved a quicker water-tight anastomosis and decreased the risk of late problems.     

Cystic fibrosis presenting with bilateral facial palsy.

A 15-week old male infant presented with bilateral lower motor neuron facial palsy of unknown cause. Subsequently his growth deteriorated and he developed progressively worsening cough and wheeze. A diagnosis of cystic fibrosis was confirmed and hypovitaminosis A detected. Improvement of the facial palsy was noted following standard management of cystic fibrosis including vitamin A supplementation.     

Synthesis and biological activity of 5-(2,2-difluorocyclopropyl)-2'-deoxyuridine deoxyuridine diastereomers.

The synthesis of the two diastereomers (9 and 10) of 5-(2,2-difluorocyclopropyl)-2'-deoxyuridine are described. Their antiviral and cytotoxic activities were determined, in comparison with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 5-fluoro-2'-deoxyuridine (FDU), respectively. 5-[(1R)-2,2-Difluorocyclopropyl]-2'-deoxyuridine (10) was the most active antiviral agent against HSV-1 (IC50 = 5 micrograms/ml) relative to BVDU (IC50 = 0.082 micrograms/ml), and cytotoxic agent in the CCRF-CEM (IC50 = 230 microM) screen relative to FDU (IC50 = 4.7 x 10(-3) microM). The 5-[(1S)-2,2-difluorocyclopropyl] diastereomer was inactive in both screens. Partition coefficients (P) and affinity for the mouse erythrocyte nucleoside transporter (Ki) were not determinants of antiviral or cytotoxic activities. However, the (1R)-diastereomer (10) was more resistant to glycosidic bond cleavage by thymidine phosphorylase than the (1S)-diastereomer (9).     

Alterations in cholinergic and non-cholinergic neurotransmitter receptor densities in transgenic Tg2576 mouse brain with beta-amyloid plaque pathology.

Cholinergic deficits in Alzheimer's disease are accompanied by a number of alterations in other transmitter systems including glutamate, noradrenaline and serotonin, suggesting the involvement also of other neurotransmitter systems in the pathogenesis of the disease. To address the question whether beta-amyloid may contribute to these deficits, brain tissue from transgenic Tg2576 mice with Alzheimer plaque pathology at ages of 5 (still no significant plaque load) and 17 months (moderate to high cortical beta-amyloid plaque load) were examined for a number of cholinergic and non-cholinergic markers. Transgenic mice with no significant plaque load demonstrated reduced hemicholinium-3 (HCh-3) binding to choline uptake sites in anterior brain regions as compared to non-transgenic littermates, while in aged transgenic mice with high number of plaque deposits decreased HCh-3 binding levels were accompanied by increased vesicular acetylcholine transporter binding in selected cortical brain regions. In aged transgenic mice GABA(A), NMDA, AMPA, kainate, and beta-adrenergic as well 5-HT(1A)- and 5-HT(2A)-receptor binding levels were hardly affected, whereas alpha(1)- and alpha(2)-adrenoceptor binding was increased in selected cerebral cortical regions as compared to non-transgenic littermates. The development of changes in both cholinergic and non-cholinergic markers in transgenic Tg2576 mouse brain already before the onset of progressive plaque deposition provides in vivo evidence of a modulatory role of soluble beta-amyloid on cortical neurotransmission and may be referred to the deficits in learning and memory observed in these mice also before significant plaque load.     

Improved results of allogeneic bone marrow transplantation for advanced hematologic malignancy using busulfan, cyclophosphamide and etoposide as cytoreductive and immunosuppressive therapy.

Twenty-four patients between the ages of 8 and 48 years (median 27.5) with high-risk for relapse hematologic malignancy received a marrow transplant from an HLA and MLC compatible sibling donor after chemotherapy with busulfan, 4 mg/kg/day for 4 days by mouth, cyclophosphamide 60 mg/kg/day i.v. for 2 days, and etoposide 60 mg/kg i.v. over 4 h on the first day of cyclophosphamide treatment (BU/CY/VP). Toxicity consisted of mucositis, skin rash, and nausea and vomiting in all patients, transient fever thought to be due to etoposide administration in 16/24 (67%) patients, and clinical veno-occlusive disease (VOD) of the liver in 4/24 (17%). There were nine deaths from causes other than recurrent disease in the first 100 days after transplant and two deaths after day 100, a total transplant mortality of 11/24 (46%). Three patients relapsed, but 10/24 (40%) remain alive and disease free 26-182 weeks (median 60 weeks) from transplant. These results compare favorably with results in a group of 12 similar risk patients treated with total body irradiation (TBI) containing regimens during an overlapping time period. Six of the TBI patients have had persistent or recurrent disease and only two (17%) are currently alive and disease free. The probability of disease persistence or relapse is 67% in the TBI group and 20% in the BU/CY/VP group (p less than 0.02).     

Impact of nutritional status on peritonitis in CAPD patients.

OBJECTIVE: To determine the impact of nutritional status on peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) in a developing country. METHODS: 56 patients with end-stage renal disease on CAPD were randomly selected for this study. These patients were assessed for nutritional status and peritonitis episodes. Nutritional parameters were assessed by anthropometry, diet, body mass index (BMI), Nutritional Risk Index (NRI), serum albumin level, and Subjective Global Assessment (SGA). Based on SGA, patients were categorized into either group 1 (malnutrition, n = 31) or group 2 (normal nutritional status, n = 25). Peritonitis was considered the primary outcome and was compared between the two groups. RESULTS: Demographic profiles, Kt/V, creatinine clearance, and mean follow-up of the two groups were similar. Number of peritonitis episodes was significantly higher in patients with malnutrition (25/31) compared to patients with normal nutritional status (4/25) (p = 0.001). Mean peritonitis rate per patient per year was also significantly higher in patients with malnutrition (0.99 +/- 1.07) compared to patients with normal nutritional status (0.18 +/- 0.42) (p = 0.007). On univariate analysis, malnutrition based on SGA (p = 0.009), NRI (p = 0.02), serum albumin level (p = 0.005), and calorie intake (p = 0.006) was a significant predictor of peritonitis. On multivariate Cox regression analysis, only SGA (p = 0.001, odds ratio 0.08, 95% confidence interval 0.02-0.36) was found to be a significant predictor of peritonitis. On general linear model, the observed power of prediction of peritonitis was 0.96 based on SGA. On Kaplan-Meier survival analysis, peritonitis-free survival in patients with normal nutrition (42 months) was significantly higher compared to patients with malnutrition (21 months) based on SGA (log rank p = 0.003). CONCLUSION: We conclude that peritonitis rate is high in patients with malnutrition and that malnutrition indices, especially SGA, can predict the peritonitis rate in CAPD patients.     

Reverse coitus: mechanism of urethral injury in male partner

Reverse coitus, a rarely used sexual position, makes the male urethra more vulnerable to injury from the pubic arch and symphysis pubis of the female partner. Severe pain, bleeding and immediate detumescence were observed in 3 patients. The lesion usually occurred at the fossa navicularis, responded well to conservative management and did not hinder micturition. Potency has been well preserved in all 3 patients.